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De presynaptische α- receptor, een mogelijk aangrijpingspunt voor farmaca

The presynaptic α- adrenoceptor, a possible target for drugs

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Abstract

The actual knowledge regarding presynaptic mechanisms in general and the model of the presynapticα-adrenoceptor in particular is reviewed in this paper. Attention is being paid to (animal) models in which presynapticα-adrenoceptors have been studied.

From these investigations it is concluded, that the ratio of the activities ofα-adrenoceptor agonists and antagonists at pre- and postsynaptically locatedα-adrenoceptors considerably depends upon the experimental model used. It is also clear that the presynapticα-adrenoceptors differ in various species and also show a dissimilarity within one species. Furthermore, presynapticα-adrenoceptors are not identical to postsynaptic ones. The effect of the presynapticα-adrenoceptor is brought about by a limitation of the concentration of the free, intraneuronal calcium. This also accounts for the frequency-dependence of the presynaptic response. The influence of the concentration of noradrenaline in the synaptic cleft, the inhibition of the neuronal uptake, the width of the synaptic cleft, the frequency of stimulation and the number of stimuli will be discussed.

The possible role which central, presynapticα-adrenoceptors may play in the mechanism of the antihypertensive effect of clonidine is discussed. Finally, it is concluded that the physiological significance of presynapticα-adrenoceptors in the periphery is not yet clear. However, an involvement is plausible at low activity of the nervous system. Central presynapticα-adrenoceptors are presumably of importance in determining behavioural processes but they probably play no substantial part in the central mechanism which induces a decrease in blood pressure. The importance of the presynaptic receptors as a target for drugs which owe their action on the peripheral or central nervous system is discussed.

Samenvatting

Dit artikel bevat een overzicht van de huidige kennis aangaande presynaptische mechanismen in het algemeen en het model van de presynaptischeα-receptor in het bijzonder. Er wordt aandacht besteed aan (dier)modellen waarin presynaptischeα-receptoren zijn onderzocht. Uit deze onderzoekingen wordt geconcludeerd dat de verhouding tussen pre- en postsynaptische activiteit vanα-adrenerge agonisten en antagonisten sterk afhangt van de experimentele opzet, dat de presynaptische α-receptoren speciesverschillen vertonen maar ook in één species kunnen verschillen, en dat presynaptischeα-receptoren niet identiek zijn aan postsynaptische. Het effect van de presynaptische a-receptor komt tot stand door een beperking van het vrije intraneuronale ionogene calcium, hetgeen tevens de frequentie-afhankelijkheid van het presynaptische effect verklaart. De invloed van de nor-adrenaline-concentratie in de synaptische spleet wordt beschouwd, evenals het belang van de remming van de neuronale opname, de breedte van de synaptische spleet, de stimulatie-frequentie en het aantal stimuli.

De mogelijke rol van centrale presynaptischeα-receptoren in het mechanisme van het antihypertensieve effect van clonidine wordt besproken. Tenslotte wordt geconcludeerd dat de fysiologische betekenis van presynaptischeα-receptoren in de periferie nog niet duidelijk is, alhoewel deze betekenis bij een lage activiteit van het zenuwstelsel zeer waarschijnlijk lijkt te zijn. In het centrale zenuwstelsel zijn de presynaptischeα-receptoren misschien van belang voor gedragsprocessen maar waarschijnlijk niet voor een bloeddrukverlagend effect. Het belang van de presynaptische receptoren als aangrijpingspunt van geneesmiddelen die via het perifere of centrale zenuwstelsel werken, wordt besproken.

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  1. Vakgroep Farmacotherapie, Laboratorium voor Farmacie, Universiteit van Amsterdam, Plantage Muidergracht 24, Amsterdam

    B. Wilffert,  P. B. M. W. M. Timmermans &  P. A. van Zweeten

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  1. B. Wilffert
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  2. P. B. M. W. M. Timmermans
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Wilffert, B., Timmermans, P.B.M.W.M. & van Zweeten, P.A. De presynaptische α- receptor, een mogelijk aangrijpingspunt voor farmaca. Pharmaceutisch Weekblad Scientific Edition 1, 245–255 (1979). https://doi.org/10.1007/BF02293196

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